OVERALL ABSTRACT The Center for Magnetic Resonance Research (CMRR) has pioneered many of the MR methods that are critical in contemporary biomedical research including (but not limited to) the introduction of UHF instrumentation and accompanying techniques that overcome its challenges, accelerated MR imaging approaches, and many of the methods used to obtain biochemical information in vivo using spectroscopy and multinuclear capabilities. To continue the tradition of innovation, the long term goal of this Center proposal is to establish a national resource for enabling ultrahigh field (UHF, mostly 7T and above), magnetic resonance imaging (MRI) technologies to advance biomedical research and discovery. Towards building this P41 center, several technical research and development (TRD) projects are proposed that will work synergistically to realize the potential of our unique imaging resources. TRD1 involves the development of a multimodal imaging platform allowing simultaneous optical imaging, an invasive technology capable of visualizing neuronal activity at the single neuron and synapse level, with non-invasive MRI methods which provide high resolution functional MRI and connectivity data over the entire brain but at a coarser spatiotemporal resolution. This platform will provide unprecedented opportunities for detailed studies of brain function underlying behavior and inform future human studies using MRI alone. TRD2 focuses on establishing a sensitive molecular imaging platform combining novel systems solutions and advanced strategies to perform multinuclear MRI spectroscopy and imaging studies. This system will provide unparalleled sensitivity to probe molecular parameters to characterize tissue through molecular dynamics, spatial distributions of functional metabolic parameters and advanced multinuclear studies. TRD3 develops reconstruction strategies supporting highly accelerated high-resolution imaging approaches while incorporating methods to reduce the impact of physiologic motion and noise. These reconstruction methods advance the field by overcoming what otherwise would be limiting factors with respect to achievable temporal and spatial resolutions. TRD4 provides critical engineering solutions addressing both 1) radiofrequency (RF) coil (i.e. antennae) designs and safety for sensitive high resolution imaging at UHF without which the systems conceived of in TRD1 and TRD2 could not be realized and 2) methods to image around implants by minimizing heating and artifacts which if not addressed would limit the access of the UHF imaging to a large section of the population. As described, these projects can tackle the fundamental challenges of UHF. Only when these challenges are addressed can we develop the new approaches to truly advance basic and clinical translational research. In fact it is exactly this cycle of development and discovery that inspired, then justified, the spending of time and resources to develop, build and site the 10.5T system at our center. While the 10.5T scanner is at the center of the proposed developments, the impact of this Center on biomedical research will extend 7T and below as well as to fields beyond MRI (cognitive science, neuroscience, senescence, musculoskeletal disorders, neurological disorder, cancer among others).